1. Field of the Invention
The present invention provides compositions, methods and vaccines that are multivalent for use against viral, bacterial and others diseases, in particular, compositions and methods for the manufacture of multivalent conjugate vaccines using VLP's.
2. Description of the Background
Infections caused by viral, bacterial or other agents occur in a variety of animals. Infections are generally species specific and classified into distinct groups based on the host that they infect which can include multiple serotypes. Multivalent vaccines have been developed in an attempt to vaccinate against all or the most likely serotypes of the infectious agent. A multivalent pneumococcal polysaccharide vaccine, Prevnar 13, has been used in preventing pneumococcal disease. Prevnar 13 contains thirteen pneumococcal serotypes, serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F. There still exist nine additional serotypes that could be pathogenic, and thus, the Prevnar 13 vaccine does not address infections caused by these additional nine serotypes. Another problem exists in that these new serotypes do not have a human host. As vaccine development takes many years, there exists an urgency to develop a suitable vaccine as soon as possible.
Virus-like particles (VLPs) have been shown to be useful as vaccines against a variety of infectious agents including viral and bacterial infections. VLP's are formed from the self-assembly of structural proteins of selected groups of viruses. These proteins self-assembly into a capsule, but, as none of the replicating nucleic acids are present, the VLP cannot replicate virus genome and create more or otherwise infectious virus particles. VLPs are strictly non-infectious and generally harmless to the environment.
When VLPs are formed in the presence of an antigenic molecule, the VLP's become delivery vehicles for the antigen or, in other words, effective vaccines. VLPs can possess an antigenicity similar to the parent virus from which the structural components were obtained or derived and therefore useful as vaccines against that particular virus infection. VLP's are generally useful as vaccines by possessing antigen within the components of the VLP. This allows for foreign antigens to be exposed on their surfaces. Other VLPs have been used as carriers for foreign antigens, including non-protein antigens, via chemical conjugation. However, decorating VLPs with target-antigens by genetic fusion or chemical modification is time-consuming and often leads to capsid misassembly or antigen misfolding, hindering generation of protective immunity.
Presently available vaccines, such as vaccines against Streptococcus pneumoniae, involve a multivalent polysaccharide conjugate vaccine using a protein carrier. Currently there is a limitation on the number of antigen conjugates which creates a zone of no protection to the balance serotypes. As the current vaccine prevents infection caused by pathogens specific to the vaccine antigens, pathogens not antigenically represented in the vaccine become more predominant. In such a circumstance there would be no protective vaccine available for a considerable time which would include the time required to identify the new pathogen, to identify and characterize target antigens, and to develop a new vaccine. Also the current issue is the single protein used as a carrier protein. The protein component in the conjugate is twice the polysaccharide quantity and starts becoming a huge number with an increase in valency. For multivalent vaccine containing many serotypes, the protein load for the patient can be enormous. For example, assuming that the polysaccharide antigenic portion would be required at two micrograms per dose per serotype and four micrograms of carrier protein per dose per serotype, a 23 valent vaccine would create a protein load of about 92 micrograms in a dose that could be disastrous for the patient.
Accordingly, a need exists for a vaccine that does not induce a protein overload, but is protective against all pathogenic strains and/or serotypes of a particular infectious microorganism.